Preterm birth is a major public health problem, occurring in more than half a million births per year in the US alone. A number of maternal conditions have been recognized as risk factors for preterm birth, but for the majority of cases, the etiology is not completely understood. Placental inflammation secondary to infectious or immunologic factors is believed to be one of the risk factors for preterm labor. Chlamydia species have long been known to be associated with abortion in ruminants. However, the role of C. trachomatis, the leading bacterial sexually transmitted infection (STI) in the United States and one of the most prevalent STIs in the world, in adverse pregnancy outcome in women is still debated. A number of factors, such as tryptophan starvation, have been shown to promote persistent Chlamydia infection, characterized by viable, metabolically active bacteria that fail to divide. Coincidentally, the placenta is a tissue high in indoleamine 2,3-dioxygenase (IDO), which results in the degradation of intracellular pools of tryptophan. For the placenta, this phenomenon serves to inhibit T-cell alloproliferative responses and it is felt to play an important role in maternal-fetal tolerance. The goal of this FOA is to encourage new and innovative studies of pathogens that affect placental function. To that end, we have developed the following model. Lower reproductive tract infection with C. trachomatis can ascend to the level of the placenta, and in a subset of pregnant women, develop into a persistent form that can drive low grade inflammation in the surrounding tissue. We hypothesize that persistent infection of the placenta with Chlamydia spp. can trigger or promote preterm birth and impair fetal development secondary to this chronic inflammation, leading to placental dysfunction, growth restriction of the fetus, and preterm birth. The goal of this work is to: (1) Characterize the immunologic framework of the placenta and its ability to respond to Chlamydia spp.~ (2) Determine the mechanism by which Chlamydia infection of placental tissue can lead to chronic inflammation and placental dysfunction~ and (3) Determine the clinical association between infection with Chlamydia spp. and adverse pregnancy outcomes. We believe that our data will identify a treatable risk factor for preterm labor, which could lead to changes in clinical care an improved pregnancy outcomes. PUBLIC HEALTH RELEVANCE: More than half a million babies are born prematurely each year in the U.S. While survival rates for these babies have improved, many remain with long-term health problems. Most cases of premature delivery are unexplained, but it is believed that infection in the womb may play a role. We want to determine if the common venereal disease known as Chlamydia plays any role in early delivery of babies. If so, then changes in screening and treatment of pregnant women for this infection could decrease the number of premature babies.